Ultraviolet B radiation activates NF-κB and induces iNOS expression in HR-1 hairless mouse skin: role of IκB kinase-β

Mol Carcinog. 2011 Apr;50(4):310-7. doi: 10.1002/mc.20646.


Exposure to ultraviolet B (UVB) radiation is known to cause inflammatory tissue damage and skin cancer. One of the molecular links between inflammation and cancer is the eukaryotic transcription factor nuclear factor-kappaB (NF-κB), which is known to regulate expression of various pro-inflammatory genes including inducible nitric oxide synthase (iNOS). The present study was aimed at elucidating the molecular mechanisms underlying UVB-induced NF-κB activation and iNOS expression in hairless mouse skin. Irradiation of male HR-1 hairless mouse skin with UVB (5 kJ/m(2) ) resulted in increased degradation of IκBα, nuclear translocation of p65 and p50, and the DNA binding of NF-κB. Exposure to UVB radiation induced the phosphorylation and the catalytic activity of an upstream kinase IκB kinase-β (IKKβ). Pharmacological inhibition of IKKβ attenuated UVB-induced NF-κB activation in mouse skin. Irradiation of mouse skin with UVB also increased phosphorylation of extracellular signal-regulated kinase (ERK) and p38 mitogen-activated protein (MAP) kinase. Pretreatment with SC-514, a specific inhibitor of IKKβ, attenuated UVB-induced phosphorylation of ERK and p38 MAP kinase. A kinetic study showed that UVB significantly increased the expression of iNOS in mouse skin at 6 h postirradiation, which was abrogated by pretreatment with SC-514. In conclusion, the upstream kinase IKKβ is involved in UVB-induced activation of MAP kinases and NF-κB, and expression of iNOS in mouse skin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Active Transport, Cell Nucleus
  • Animals
  • Blotting, Western
  • Cell Nucleus / metabolism
  • Electrophoretic Mobility Shift Assay
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • I-kappa B Kinase / antagonists & inhibitors
  • I-kappa B Kinase / metabolism
  • I-kappa B Proteins / metabolism
  • Male
  • Mice
  • Mice, Hairless
  • NF-KappaB Inhibitor alpha
  • NF-kappa B / metabolism*
  • NF-kappa B p50 Subunit / metabolism
  • Nitric Oxide Synthase Type II / metabolism*
  • Oligonucleotides / genetics
  • Oligonucleotides / metabolism
  • Phosphorylation / radiation effects
  • Protein Binding / radiation effects
  • Skin / metabolism
  • Skin / radiation effects*
  • Thiophenes / pharmacology
  • Transcription Factor RelA / metabolism
  • Ultraviolet Rays*
  • p38 Mitogen-Activated Protein Kinases / metabolism


  • I-kappa B Proteins
  • NF-kappa B
  • NF-kappa B p50 Subunit
  • Nfkbia protein, mouse
  • Oligonucleotides
  • Rela protein, mouse
  • SC 514
  • Thiophenes
  • Transcription Factor RelA
  • NF-KappaB Inhibitor alpha
  • Nitric Oxide Synthase Type II
  • I-kappa B Kinase
  • Extracellular Signal-Regulated MAP Kinases
  • p38 Mitogen-Activated Protein Kinases